Our broad goal is to understand the circuits that link foveal cones to ganglion cells. Structural studies during the current period show the fovea to harbor multiple ganglion cell arrays. We suggest that each array signals a particular aspect of the visual scene and propose the following correspondences: high spatial frequency= midget (P) cell; low temporal frequency= parasol (M) cell; high temporal frequency= garland cell (M); hue= blue-yellow cell, red-green cell. We now plan to elucidate circuits for the remaining ganglion cells in our EM library and thus identify all the parallel channels from fovea to brain. We also plan to test these hypotheses by functional imaging of identified synapses: incubate retina with peroxidase tracer and briefly present a specific spatio-temporal-chromatic pattern to evoke exocytosis. As fused synaptic vesicles are retrieved by endocytosis, they sequester tracer which is fixed, and then visualized by confocal and electron microscopy. The ratio of labeled vesicles in different types of bipolar and amacrine synapse measures their relative release to a given stimulus. This approach, now being developed for a color-opponent circuit in guinea pig retina, will be applied to homologous circuits in primate retina. Finally, we plan to determine how the cGMP-gated channel contributes to a ganglion cell s visual response. Current through this channel is enhanced by nitric oxide and suppressed by glutamate through a novel mechanism (AMPA receptor coupled to a G-protein). We will identify the types of ganglion cell that express this current and determine which visual stimuli evoke and suppress it. The fovea occupies only two mm2 (0.3 percent) of the retina, but it supplies half of the visual cortex and is thus key to human vision. Knowing the functional architecture of its multiple, parallel circuits will help understand visual impairment (from conditions such as macular edema and age-related macular degeneration) and will ultimately contribute to the design of a retinal prosthesis.